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Naringenin, a Food-Derived Flavanone, Suppresses ITGA11-Associated Gastric Cancer Progression via the FAK/PI3K/AKT/mTOR Axis
by
and
Qiang Li
1, 
Guiyang Ye
1,
Fangfang Chen
2,
Qiushuang Wang
1,
Junfeng Yan
1,
Yi Wang
3,4,* and
Qiang Tong
1,* 1
Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan 430060, China
2
Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3
Translational Clinical Immunology Key Laboratory, Sichuan Provincial People’s Hospital, Chengdu 610072, China
4
Department of Dermatology Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(11), 1712; https://doi.org/10.3390/cancers18111712 (registering DOI)
Submission received: 24 April 2026
/
Revised: 21 May 2026
/
Accepted: 22 May 2026
/
Published: 24 May 2026
(This article belongs to the Section Cancer Pathophysiology)
Simple Summary
Gastric cancer is a common and deadly cancer, and better markers and treatment strategies are urgently needed. The tissue environment surrounding cancer cells can strongly influence how tumors grow and spread, but the molecules that help gastric cancer cells respond to this environment are not fully understood. In this study, we found that integrin alpha 11 is increased in gastric cancer and is associated with more aggressive disease and poorer patient survival. We further showed that integrin alpha 11 promotes gastric cancer cell proliferation, migration, and invasion in vivo and in vitro by activating the FAK/PI3K/AKT/mTOR signaling pathway. Importantly, we found that Naringenin may reduce these harmful effects by lowering integrin alpha 11 activity. These findings suggest that integrin alpha 11 may be a useful biomarker and potential therapeutic target, and that Naringenin may offer a promising strategy for future gastric cancer research.
Abstract
(1) Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. Aberrant remodeling of the extracellular matrix (ECM) is a hallmark of GC progression; however, the mechanisms by which GC cells sense and exploit ECM cues remain unclear. (2) Methods: ITGA11 was identified through integrative bioinformatic analyses. Its expression, clinical significance, and association with ECM-related signatures were evaluated in GC tissues and public datasets. The function of ITGA11 and its role in regulating the FAK/PI3K/AKT/mTOR pathway were investigated using in vitro and in vivo assays, and the inhibitory effect of Naringenin on ITGA11-associated oncogenic activity was assessed. (3) Results: ITGA11 was upregulated in GC tissues and correlated with an ECM-related gene signature, aggressive clinicopathological features and poor patient survival. ITGA11 promoted malignant phenotypes of GC cells in vitro and in vivo. Importantly, molecular docking and target engagement assays suggested a potential interaction between Naringenin and ITGA11. Functional experiments showed that Naringenin attenuated ITGA11-associated oncogenic activity by reducing ITGA11 levels, suppressing pathway activation, and inhibiting malignant phenotypes. (4) Conclusions: Our findings identify ITGA11 as a potential prognostic biomarker and functional driver of GC progression and suggest that Naringenin may represent a promising bioactive compound for modulating the ITGA11/FAK/PI3K/AKT/mTOR axis in GC.
Keywords:
Naringenin; gastric cancer; ITGA11; FAK/PI3K/AKT/mTOR axis
